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Clinical Trials, U.S.: Eye Conditions
Clinical Trials, U.S.: Eye Conditions
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Clinical Trials, U.S.: Eye Conditions
Retinopathies pertain to vascular conditions that involve the eye, often leading to blindness. Research on cell-based therapy has resulted in the identification of self-renewing cells that could be utilized to replace lost cells of the retina, including associated vascular and neuronal tissues. Interestingly, there are at least four types of stem cells that could be employed for cell-based therapy of eye conditions.
Eye Diseases Involve Loss of Pericytes and Vascular Tissues
Diabetic retinopathy pertains to the dysfunctional regulation of the blood vessels of the retina, resulting in damage to the underlying vascular tissues and endothelial cells of the eye, ultimately leading to blindness. It is considered the most common complication associated with diabetes, affecting approximately 7 million individuals in the United States alone. Diabetic retinopathy is considered the main cause of blindness in American adults. The disease initiates with the loss of pericytes, which are cells that enfold endothelial cells of small vascular tissues such as the capillaries and venules. Similar to its role in the rest of the body, pericytes in the eye control cellular homeostasis, as well as normalize blood flow to and from the ocular organ. In diabetic retinopathy, loss of pericytes occurs, coupled with the thickening of the basement membrane, as well as disruption of the endothelial cell and abnormally high levels of angiogenesis involving the retina. These changes result in the development of edema and neuronal death, which then results in blindness.
In age-related macular degeneration, the macula, as well as the retinal pigment epithelia of the eye, accumulates waste material, resulting in the deposition of amorphous substances that are technically referred to as drusen. Furthermore, the retinal pigment epithelia undergo degeneration, resulting in a disruption and eventual loss of central vision. Wet age-related macular degeneration pertains to the development of new vascular tissues in the subpigment epithelial layer, as well as the subretinal spaces, which is mainly attributable to the disorganization of membranes. This destruction in tissue organization results in leaky vascular tissues, which in turn results in edema. Further accumulation of fluids in subretinal spaces then affects vision, ultimately causing blindness.
The potential of using stem cells for the treatment of diabetic retinopathy stems from the principle that these self-renewing cells could replace lost pericytes that are associated with the disorder. The use of stem cells to maintain major tissues of the body, including that of the retina, might therefore be a promising therapeutic approach for the most common eye condition. There are currently four major stem cell populations that could be employed for cell-based therapy of diabetic retinopathy. Retinal stem cells have the ability of generating photoreceptors, as well as neurons that associate with the retina. Glial stem cells have the capacity to mature into retinal glia, and possibly neurons, whereas retinal pigment epithelial stem cells can inherently replace damaged cells and tissues, as well as undergo induction and differentiate into photoreceptors. Myeloid or endothelial progenitor cells and induced pluripotent stem cells may also be employed for the reconstruction of the vascular tissues of the retina. These specific stem cells are also capable of engaging in rescuing neurotrophic tissues.
Recent studies have shown that an additional group of stem cells, namely mesenchymal stem cells, may also be used in cell-based therapies for diabetic retinopathy. These cells are derived from bone marrow and peripheral blood, as well as cord blood. Research has shown that CD90+ cells from the bone marrow could be induced to differentiate into photoreceptors. In addition, adipose stromal cells introduced into damaged tissues of the cornea have been reported to undergo differentiation into keratocytes, thus facilitating stromal regeneration and replacement of diseased corneas. It appears that adipose stromal cells have the capacity to undergo differentiation into a wide variety of cells, including pericytes that have been implicated in the pathogenesis of diabetic retinopathy. Adipose stromal cells are also capable of secreting different factors that act against apoptosis and promote angiogenesis. These activities then decrease the severity of tissue loss and promote the repair of damaged tissues. These initial studies thus prompted scientists to conduct more extensive investigations involving adipose stromal cells as a potential approach in various cellular therapies.
Clinical Trials Involving the Use of Stem Cells in Eye Disorders
The first attempt to transplant embryonic retinal cells was conducted in 1959 and involved rats as animal models. By the 1980s, retinal pigment epithelial cells were cultured in the laboratory and later transplanted into primate eyes for vitrectomy. In the 1990s, the first human transplant experiment was conducted and utilized retinal pigment epithelial cells; however, this showed a low success rate, triggering extensive studies that focused on decreasing the rejection rates and safety of the transplant technique. To date, at least 230 transplantation procedures have been conducted using retinal pigment epithelial cells.
Approximately 200 clinical trials are currently being conducted using mesenchymal stem cells in various diseases, ranging from connective tissue disorders to heart diseases. In terms of eye conditions, mesenchymal stem cells have been employed in the treatment of blindness caused by diabetic neuropathy (NCT01518842). In 2012, the United States Food and Drug Administration approved the clinical trial that would determine the safety of embryonic stem cells for age-related macular degeneration. Another clinical trial, NCT01344993, investigated the effectiveness of embryonic stem cells as cell-based therapy for age-related macular degeneration, particularly those involving the disruption of central vision. Initial results of the clinical trial showed that two patients showed vision improvement, and at the fourth month of follow-up, neither patient showed signs of vision loss. However, it is also important to understand that the application of embryonic stem cells in various medical conditions have been under intense scrutiny for years, specifically in terms of ethics, efficacy, and safety.
The study included 12 patients positively diagnosed with age-related macular degeneration and another 12 patients with Stargardt’s disease, which is considered to be the earlier stage of macular degeneration. Stargardt’s disease is genetically transmitted and is associated with proteins that are responsible for the phototransduction cycle of vision. The participants of the clinical study received subretinal injections of retinal pigment epithelial cells, at a density of 50,000 cells. The other treatment arms of the study received
